Effect of the peroxisome proliferator‐activated receptor gamma (PPARγ) agonist Rosiglitazone on the hypothalamic GT1‐7 cell line

Polycystic ovary syndrome (PCOS) is a major cause of infertility in women and is linked to obesity and insulin resistance. Rosiglitazone, a PPARγ agonist, increases insulin sensitivity and improves PCOS and diabetes. PPARγ ligands have also been found to affect the hypothalamus‐pituitary‐gonadal axis, although their site and mechanism of action are not entirely known. The aim of this study was to determine the effects of rosiglitazone on insulin and kisspeptin stimulation of GT1‐7 hypothalamic GnRH neurons. Timecourse and dose response experiments were conducted using 24 hour pretreatment of rosiglitazone or vehicle, and with either insulin or kisspeptin stimulation. Akt and ERK phosphorylation were analyzed with Western Blot and GnRH mRNA expression was analyzed with RT‐QPCR. Preliminary results indicated that treatment with rosiglitazone increased insulin‐induced phosphorylation of Akt in GT1‐7 cells. Maximal stimulation occurred between 10 and 15 minutes, and an insulin concentration of 10 nM. Kisspeptin alone increased GnRH mRNA, with maximal stimulation at 1 nM, as reported by others. Furthermore, rosiglitazone appears to increase kisspeptin induced GnRH mRNA. In conclusion, rosiglitazone appears to have a direct role in regulating hypothalamic GT1‐7 neurons by acting as an insulin sensitizer and modulating the effects of kisspeptin. Supported by NIH grant U54HD12303. VH was supported by Julia Brown Undergraduate Research Scholarship.